Rifampin-Induced Minimal Change Disease

Introduction: Latent Mycobacterium tuberculosis affects around 25% of the international and 3.1% of the American population. One of the most common treatments is rifampin. In the past, there have been cases of rifampin-associated interstitial nephritis and nephrotic diseases which have typically resolved with cessation of the offending agent and a short course of steroids. Although rituximab and calcineurin inhibitors (CNI) are effective treatments in frequently relapsing/steroid-dependent patients with primary minimal change disease (MCD), this is the first reported case of their use in rifampin-induced MCD. Case Description: This is a 33-year-old female with a history of latent tuberculosis who presented to the hospital with edema, nausea, and vomiting. One month before, she was initiated on rifampin 600mg daily with a planned 4-month course. On initial blood work, she had an elevated creatinine of 1.46mg/dL from a baseline of 0.7mg/dL, and an albumin of 2.1g/dL. Urinalysis revealed 3+ protein and 2+ blood. The urine protein-creatinine ratio was 26.2mg/mg. She had negative anti-MPO, anti–PR3, ANA, anti-dsDNA, and anti-GBM antibodies, and normal C3 and C4 levels. Renasight genetic testing revealed no known disease-causing variants. Rifampin was discontinued. Solumedrol 500mg was given and followed with prednisone at 1mg/kg. A kidney biopsy was obtained. Light microscopy was unremarkable, but electron microscopy revealed diffuse podocyte foot process effacement, vacuolization of cell bodies, and villous transformation of the cytoplasm consistent with MCD. Creatinine peaked at 4.18 mg/dL before trending down to baseline. Prednisone was rapidly tapered. Once steroid therapy was completed, the proteinuria returned and prednisone was resumed. Due to refractory proteinuria, she received rituximab 1g twice two weeks apart and tacrolimus (target trough of 3-5mg/dL) and a short steroid taper owing to weight gain and hypertension. Discussion: When evaluating patients with drug-induced nephrotic syndrome, clinicians should be aware that removing the offending agent is not always enough.This case shows that the principles of treating primary MCD can apply to secondary MCD. This patient with relapsing disease eventually responded to rituximab and CNIs. It is important to monitor proteinuria in these patients to choose the most appropriate treatment.